Serotonergic conversion of MPTP and dopaminergic accumulation of MPP+

FEBS Letters

Gessner, W.¹  Shen, R.-S.²  Brossi, A.¹  Abell, C.W.² 

[1] Laboratory of Chemistry, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20205, USA;Department of Human Biological Chemistry and Genetics, Division of Biochemistry, University of Texas Medical Branch, Galveston, TX 77550, USA

关键词: MPTP;    MPP+;    Neurotoxin;    Parkinsonism;    Dopamine uptakef;   

DOI  :  10.1016/0014-5793(85)81028-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

[³H]MPP⁺ had lower K _m and higher V _max values for its accumulation in rat brain synaptosomes than did [³H]MPTP. The kinetic parameters favored the uptake of [³H]MPP⁺ in the striatum to that in hypothalamus, whereas they were equally favorable for the uptake of [³H]MPTP in both regions. Hypothalamic uptake of [³H]MPTP and [³H]MPP⁺ was inhibited by desipramine, imipramine, norepinephrine, and serotonin. Striatal uptake of [³H]MPP⁺ and [³H]MPTP was blocked by nomifensine and dopamine. These results support the concept that MPTP accumulates in serotonergic neurons where it is oxidized by monoamine oxidase B to MPP⁺, which is released and then is selectively accumulated in dopaminergic neurons via the dopamine uptake system.

【 授权许可】

Unknown